Diisopropylethylamine → HCID 11671647, compound

HRID 1028492Notes

Reaction equation

HRID 1028492 reaction equation
[F:1][C:2]([F:40])([F:39])[C:3]1[CH:4]=[C:5]([CH:13]([OH:38])[CH2:14][NH:15][CH2:16][C:17]2[CH:22]=[C:21]([C:23]([F:26])([F:25])[F:24])[CH:20]=[CH:19][C:18]=2[C:27]2[CH:32]=[C:31]([CH:33]([CH3:35])[CH3:34])[CH:30]=[CH:29][C:28]=2[O:36][CH3:37])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.CCN(C(C)C)C(C)C.Cl[C:51](Cl)([O:53]C(=O)OC(Cl)(Cl)Cl)Cl.C([O-])(O)=O.[Na+]>C(Cl)Cl>[F:1][C:2]([F:39])([F:40])[C:3]1[CH:4]=[C:5]([CH:13]2[O:38][C:51](=[O:53])[N:15]([CH2:16][C:17]3[CH:22]=[C:21]([C:23]([F:24])([F:25])[F:26])[CH:20]=[CH:19][C:18]=3[C:27]3[CH:32]=[C:31]([CH:33]([CH3:35])[CH3:34])[CH:30]=[CH:29][C:28]=3[O:36][CH3:37])[CH2:14]2)[CH:6]=[C:7]([C:9]([F:11])([F:10])[F:12])[CH:8]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 94429TriphosgeneHCID 516892Sodium BicarbonateHCID 86603405HCID 86603405, compound

Product 1

HCID 11671647HCID 11671647, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 1-[3,5-bis(trifluoromethyl)phenyl]-2-({[5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}amino)ethanol (31.9 mg, 0.0551 mmol) in CH2Cl2 (5 mL) at 0° C. was added DIPEA (67 μL, 0.386 mmol), followed by triphosgene (8.2 mg, 0.0276 mmol). The reaction was stirred at 0° C. for 30 minutes. The reaction was then poured into saturated NaHCO3 (15 mL) and the mixture was extracted with EtOAc (50 mL). The organic layer was washed with brine (15 mL), dried over Na2SO4, filtered, and concentrated. Purification of the residue by flash chromatography (20% EtOAc/hexanes) afforded 5-[3,5-bis(trifluoromethyl)phenyl]-3-{[5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}-1,3-oxazolidin-2-one. Rf=0.32 (25% EtOAc/hexanes). LCMS=606.3 (M+1)+. 1H NMR (CD2Cl2, 500 MHz) (atropisomers present in 1:1 ratio, doubling of some peaks) δ 7.90 (s, 1H), 7.77 (s, 2H), 7.57-7.62 (m, 2H), 7.37 (d, J=8.0 Hz, 1H), 7.27 (m, 1H), 6.98 (s, 1H), 6.93 (dd, J=8.4, 3.2 Hz, 1H), 5.42-5.53 (m, 1H), 4.15-4.59 (m, 2H), 3.72 & 3.73 (2 singlets, 3H), 3.05-3.65 (m, 2H), 2.88 (m, 1H), 1.19-1.23 (m, 6H).

Workup

  1. extractionthe mixture was extracted with EtOAc (50 mL)
  2. washThe organic layer was washed with brine (15 mL)
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification of the residue by flash chromatography (20% EtOAc/hexanes)

Sources & evidence

ORD record
ord-1df8b32b76e54d73af0f40298810b178
Source dataset
uspto-grants-2014_05
Patent number
US08735435B2

Reaction notes

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